JP2003277455A - Method for producing polymer particle, polymer particle and carrier for physiologically active substance - Google Patents

Abstract

<P>PROBLEM TO BE SOLVED: To provide a method for producing a polymer particle, with which a carboxy group-modified particle having a large particle diameter and a uniform diameter is obtained in excellent polymerization stability and in excellent polymerization repeatability of the particle diameter, and to obtain a polymer particle which is highly coated with a carboxylate group, not only combines with a physiologically active substance by a chemical bond in high density but also has extremely slight nonspecific adsorption of physiologically active substances except the target due to high hydrophilicity on the surface of the particle. <P>SOLUTION: The method for producing the polymer particle comprises polymerizing a polymerizable monomer containing ≥50 wt.% of a water-soluble polymerizable carboxylic acid monomer in the presence of a water-soluble radical initiator in a water medium and subjecting a vinyl monomer to emulsion polymerization in the presence of the obtained polymer. <P>COPYRIGHT: (C)2004,JPO

Description

Detailed Description of the Invention

[0001]

TECHNICAL FIELD The present invention relates to a method for polymerizing emulsion-polymerized polymer particles modified with a carboxyl group and polymer particles obtained by the method. More specifically, the present invention relates to a production method for producing a carboxyl group-modified polymer particle having a large particle diameter, which is conventionally difficult to obtain by ordinary emulsion polymerization, with a relatively uniform diameter, good polymerization stability, and good production reproducibility, and the polymer particle. In addition, the present invention contains a large amount of carboxyl groups on the surface of particles, and protein substances such as antibodies and DNA
A large amount of nucleic acid substances such as RNA or physiologically active sugar chain compounds (hereinafter referred to as physiologically active substances) can be bound by chemical bonds, and physical adsorption (non-specific adsorption) of undesired physiologically active substances is minimal. It relates to a polymer particle for a high-performance bioactive substance carrier.

[0002]

2. Description of the Related Art Polymer particles having a relatively small particle size and a relatively uniform particle size as compared with other water-based polymerization methods such as suspension polymerization method, water-based dispersion polymerization method and mini-emulsion polymerization method which have hitherto been used. It was said that there was a feature in obtaining. The standard particle size in emulsion polymerization is about 0.05 to 0.2 μm. Further, in emulsion polymerization, the control of the functional groups on the particle surface is relatively easy, so modification is performed according to various purposes and uses, and a large amount of products are industrially manufactured by the emulsion polymerization method. . However, in order to synthesize a polymer particle having a large particle diameter exceeding the above-mentioned particle diameter by emulsion polymerization, it is necessary to reduce the amount of the emulsifying agent which is a stabilizer and polymerize, and the polymerization stability is significantly deteriorated. The particle size of the polymer particles fluctuates greatly with each polymerization, resulting in poor polymerization reproducibility. Further, particularly in emulsion polymerization of carboxyl group-modified particles, the presence of the carboxyl group-containing monomer tends to further reduce the particle size. Therefore, for example, 0.4
It is possible to synthesize single-shot carboxyl group-modified polymer particles with a large particle size exceeding μm in the laboratory by emulsion polymerization method, but it is difficult to manufacture this on an industrial scale with good reproducibility, and special measures are required. Met. Further, in the use of polymer particles for a physiologically active substance carrier in which a protein substance such as an antibody, a nucleic acid substance such as DNA / RNA or a physiologically active substance such as a physiologically active sugar chain compound is bound to the surface of the particle by physical adsorption or chemical bonding, It is required that the particles have a large particle size because centrifugal sedimentation is easy when washing and refining the particles, and that the particle size is uniform because the surface properties of the particles are uniform. On the other hand, in the above technical situation regarding particle synthesis, it was difficult to synthesize polymer particles of uniform diameter and large particle diameter by emulsion polymerization method, particularly carboxyl group-modified polymer particles with good reproducibility on an industrial scale. . Polymer particles for physiologically active substance carriers must have physical adsorption of the target physiologically active substance on the particle surface by physical adsorption or chemical bonding, and then physical adsorption of other unintended physiologically active substance on the particle surface (referred to as non-specific adsorption). There should not be. For the reasons described above, there has been a demand for particles which can easily bind a target physiologically active substance to the surface of the particle and which causes non-specific adsorption of a non-target physiologically active substance thereafter as little as possible.

[0003]

DISCLOSURE OF THE INVENTION The present invention provides a carboxyl group-modified particle having a large particle diameter and a uniform diameter with good polymerization stability.
And, the production method of the polymer particles obtained with good reproducibility of polymerization of the particle diameter and highly coated with a carboxylic acid group,
It is an object of the present invention to obtain polymer particles in which not only non-specific adsorption of a physiologically active substance other than the purpose is markedly reduced because the hydrophilicity of the particle surface is high, but not only the physiologically active substance can be bound with a high density by a chemical bond.

[0004]

According to the present invention, a polymerizable monomer containing 50% by weight or more of a water-soluble polymerizable carboxylic acid monomer is polymerized in an aqueous medium by using a water-soluble radical initiator, and this polymerization is carried out. The present invention provides a method for producing an emulsion-polymerized polymer, which comprises emulsion-polymerizing a vinyl monomer in the presence of a substance, and polymer particles produced by the method.

The water-soluble and polymerizable carboxylic acid monomer in the polymerization of the carboxylic acid monomer which is the first-stage polymerization in the present invention has a solubility in water at 20 ° C. of 1 g / 100 m.
Radical-polymerizable monomers, salts and acid anhydrides thereof which are 1 or more. Specific examples include acrylic acid, methacrylic acid, itaconic acid, fumaric acid, maleic acid, maleic anhydride, and salts thereof, with itaconic acid, acrylic acid, and methacrylic acid being particularly preferred. These carboxylic acid monomers can be used in combination of two or more kinds. The monomer in the first-stage polymerization of the present invention comprises 50% by weight or more of these carboxylic acid monomers, preferably 80% by weight or more, more preferably 90% by weight or more, and most preferably carboxylic acid monomer alone. If the amount of the carboxylic acid monomer in the first-stage polymerization is less than 50% by weight, the polymerization stability of the subsequent second-stage polymerization is poor, and the particle size distribution of the obtained polymer particles is broad, so that the object of the present invention can be achieved. Can not.

The monomer other than the carboxylic acid monomer in the first-stage polymerization of the present invention is not particularly limited as long as it is a monomer that can be emulsion polymerized. Specific examples include styrene,
Aromatic vinyl compounds such as α-methylstyrene, vinyltoluene, divinylbenzene, vinylbiphenyl, divinylbiphenyl and vinylnaphthalene; methyl (meth) acrylate, ethyl (meth) acrylate, butyl (meth) acrylate, cyclohexyl (meth) acrylate, Examples thereof include (meth) acrylic acid esters such as 2-ethylhexyl (meth) acrylate. If necessary, glycidyl (meth) acrylate, vinylbenzylamine, acrylamide, methacrylamide, acrylamido-t-butylsulfonic acid, 2-sulfoethyl methacrylate, 2-methoxyethyl acrylate, chloromethylstyrene, polyethylene oxide side chain It is also possible to use a monomer having a specific functional group such as modified (meth) acrylate. The first-stage polymerization of the present invention is carried out in an aqueous medium using a water-soluble radical initiator. Specific examples of the water-soluble radical initiator that can be used here include persulfate initiators such as ammonium persulfate, sodium persulfate, and potassium persulfate, or redox initiators such as ascorbic acid / cumene hydroperoxide can be favorably used. .
In addition, 2,2'-azobisisobutyronitrile, 2,
Azo-based initiators such as 2'-azobis (2,4-dimethylvaleronitrile) can also be used. Of these, persulfate initiators are most preferred.

In the second-stage polymerization of the present invention, after the first-stage polymerization is completed, cooled and taken out, the polymer aqueous solution or dispersion is added to the second-stage reaction vessel for polymerization. it can. Alternatively, after the first stage polymerization, the second stage monomer may be added to carry out the second stage polymerization as it is. In the case of subsequent polymerization, the polymerization can be continued without lowering the temperature of the reaction vessel, and efficient production can be achieved.
The first-stage polymerization does not have to be completed, and the object of the present invention can be achieved even if the second-stage polymerization is continuously performed as long as the first-stage polymerization rate is about 25% or more. it can. The monomer for the second-stage polymerization is not particularly limited as long as it is a monomer capable of emulsion polymerization. Specific examples include aromatic vinyl compounds such as styrene, α-methylstyrene, vinyltoluene, divinylbenzene, vinylbiphenyl, divinylbiphenyl, and vinylnaphthalene; methyl (meth) acrylate, ethyl (meth) acrylate, butyl (meth). (Meth) acrylic acid esters such as acrylate, cyclohexyl (meth) acrylate and 2-ethylhexyl (meth) acrylate; unsaturated carboxylic acids such as acrylic acid, methacrylic acid, itaconic acid, fumaric acid, maleic acid and maleic anhydride Can be mentioned. If necessary, glycidyl (meth) acrylate, vinylbenzylamine, acrylamide, methacrylamide,
Acrylamide-t-butyl sulfonic acid, 2-sulfoethyl methacrylate, 2-methoxyethyl acrylate,
It is also possible to use a specific functional group-containing monomer such as chloromethylstyrene or polyethylene oxide side chain modified (meth) acrylate. Further, in the present invention, since a large amount of the carboxylic acid monomer component by the first-stage polymerization is transferred to the particle surface, it is not necessary to use the carboxylic acid monomer in the second stage, but because of the second-stage polymerization stability. It is also possible to use suitable amounts of carboxylic acid monomers. The polymerization initiator for the second-stage polymerization of the present invention may be any water-soluble radical initiator, and those shown in the first-stage polymerization can be favorably used. When the second stage polymerization is carried out subsequent to the first stage, the same initiator as the first stage initiator may be used. It is also possible to add a large amount of initiator to the first stage and polymerize, and use the remaining initiator as it is as the second stage initiator. The ratio (weight ratio) of the total monomers in the first-stage polymerization to the total monomers in the second-stage polymerization in the present invention is usually 0.2 / 99, though it depends on the kind of the first-stage carboxylic acid monomer. .8-20 /
80, preferably 0.5 / 99.5 to 15/8
5, more preferably 1/99 to 9/91. Weight ratio of first stage monomer / second stage monomer is 20/8
If it is greater than 0, the amount of water-soluble components in the second-stage polymerization is too large and the polymerization stability deteriorates. If the weight ratio of the first stage monomer / the second stage monomer is less than 0.2 / 99.8, the substantial effect of the present invention cannot be expected. Also,
The ratio of the carboxylic acid monomer to the total amount of the monomers polymerized in the first-stage polymerization and the monomers polymerized in the second-stage polymerization is 0.2 to 20% by weight, preferably 0.5.
-15% by weight, particularly preferably 1-10% by weight.

In the second stage polymerization of the present invention, the polymerization stability is relatively good due to the presence of the high carboxyl group polymer in the first stage. In the second-stage polymerization, it is also possible to carry out the polymerization basically without an emulsifier. Also,
Further, polymerization in the second stage by using an emulsifier more than necessary not only deteriorates the practical performance of the particles but also decreases the particle size and the polymerization stability is rather deteriorated. Therefore, the amount of the emulsifier used in the second-stage polymerization of the present invention is preferably 0 to 500 ppm (weight unit) in water concentration, more preferably 0 to 300 ppm, or 0.
-200 ppm.

The method of the present invention is suitable for the synthesis of large-sized polymer particles, and the average particle diameter (measurement method: electron microscopy) of the method of the present invention is usually 0.25 to 1.3 μm.
Preferably 0.35-1.2 μm, especially 0.4-1.0
Particles of μm can be obtained. The coefficient of variation (CV value) of the particle diameter here is usually 20% or less, preferably 10% or less, and particularly 6% or less.

The polymer particles of the present invention, after emulsion polymerization,
It can be used as carrier particles for medical and biological applications after adjusting the pH and, if necessary, removing residual monomers with steam strips, etc. and washing the particle surface with dialysis, ultrafiltration, centrifugation, etc. Compared with conventional carrier particles, the carrier particles of the present invention have a higher density of carboxylic acid groups on the particle surface, and the amount of the target physiologically active substance (antibody, antigen, protein, nucleic acid, sugar chain, etc.) bound by the chemical bonding method In addition to being significantly large, the non-specific adsorption of undesired physiologically active substances is extremely small due to the large hydrophilicity of the particle surface. Therefore, the particles of the present invention can be used as high-performance bioactive substance carrier particles for chemical bonding.

In the polymer particles for a physiologically active substance carrier of the present invention, a monomer having a functional group suitable for the physiologically active substance to be sensitized during use is preliminarily polymerized in the second stage during the second stage polymerization. Can be incorporated into the particle surface by being present in the latter half of the. For this purpose, carboxylic acid monomers such as methacrylic acid, acrylic acid, fumaric acid and itaconic acid, epoxy group-containing monomers such as glycidyl methacrylate, and amino group-containing monomers such as vinylbenzylamine and p-aminostyrene are used. Of these, the epoxy group is useful because it can be converted into many functional groups under the treatment conditions after the polymerization. Further, in the present invention, in the second-stage polymerization, when a radical polymerization initiator containing a specific amino group is used, the amino group of the initiator residue is present on the surface of the polymerized particles, and the protein, nucleic acid, sugar chain, etc. It can be chemically bound to a physiologically active substance.

The bioactive substance such as protein, nucleic acid or sugar chain substance can be directly bound to the surface of the polymer particle for a bioactive substance carrier of the present invention by a chemical bonding method before use.
By attaching one end of a bifunctional spacer compound to the particle surface,
By binding a physiologically active substance to the other, the physiologically active substance can be separated from the particle surface by a slight distance. When the carrier particles of the present invention are amino group-modified particles, examples of the spacer compound include ethylene glycol diglycidyl ether and its derivatives. By separating the physiologically active substance from the particle surface, it is expected that the activity of the physiologically active substance is greatly improved, approaches the value in the homogeneous solution, and sometimes exceeds it. The carrier particles of the present invention are sensitized with a physiologically active substance such as protein, nucleic acid, sugar chain substance, etc. by a chemical bonding method. As the sensitizing method, a conventional ordinary chemical bonding method process (protocol) is applied. it can.

[0013]

EXAMPLES The present invention will be described in more detail with reference to the following examples. In this example,% and parts are based on weight. Example 1 (First-stage polymerization) In a 2 L glass flask equipped with a stirrer, 1800 ml of ion-exchanged water, 0.1 g of sodium dodecylbenzenesulfonate as an emulsifier (concentration in water: 55 ppm), 2 g of itaconic acid as a carboxylic acid monomer, acrylic acid 1
g was added, nitrogen substitution was carried out while stirring at 120 rpm, and the temperature was raised to 80 ° C. When the temperature reached 80 ° C, 3 of the initiator
% Aqueous solution of potassium persulfate (16.7 g) was added, and polymerization was carried out at 80 ° C. for 0.5 hour. When the solid content concentration was measured at 0.5 hours to measure the polymerization conversion rate, the polymerization conversion rate was 4
It was 5% and the polymerization liquid was almost transparent. (Second-stage polymerization) At 0.5 hours after the start of the first-stage polymerization, 97 g of styrene was added as a second-stage monomer, and the polymerization was continued for 5 hours at 80 ° C. Polymer particles of Example 1 were obtained with good polymerization stability. After the completion of the polymerization, the reaction mixture was cooled and the solid content concentration was measured to measure the polymerization conversion rate, which was 99.5%. When the particle size was measured with an electron microscope, the average particle size was 0.65 μm,
The variation coefficient of the particle diameter was 1.2%, which was a large particle diameter and a uniform particle diameter that were difficult to obtain by ordinary emulsion polymerization. For the particles of Example 1, the pH was adjusted to 8 with 1% sodium hydroxide, the particles were settled by centrifugation at 6,000 rpm for 10 minutes, the supernatant was discarded, and the particles were redispersed with ion-exchanged water, which was repeated 3 times. Particles were purified.

Example 2 Polymerization was carried out in exactly the same manner as the first-stage polymerization in Example 1, and the polymer was cooled 1 hour after the initiation of the polymerization to obtain an aqueous polymer solution for the first-stage polymerization. The polymerization conversion rate measured from the polymerization solids is 8
It was 7%. In a 1 L glass flask equipped with a stirrer, 800 ml of the polymer dispersion of the first stage polymerization, 40 styrene
g, divinylbenzene 0.2 g, methyl methacrylate 1
Add 0 g, 5% ammonium persulfate 10 g, 120
Replace with nitrogen while stirring at rpm, raise to 75 ° C and
After the second-stage polymerization for a certain period of time, the system was cooled. The polymerization stability was good, the polymerization conversion rate was 99.8%, the particle diameter by an electron microscope was 0.58 μm, and the variation coefficient of the particle diameter was 1.5%. In Example 2, as in Example 1, particles having a large particle size and a uniform particle size were obtained with good polymerization stability.

Examples 3-9, Comparative Examples 1-3 The same procedure as in Example 1 was carried out except that the types and amounts of monomers, the amounts of polymers in the first-stage polymerization, and the amounts of emulsifiers were changed as shown in Table 1. Polymer particles of Example 3-9 and Comparative Example 1-3 were obtained.
The results are shown in Table 1. Comparative Example 1 is an example in which the same monomer composition and the same amount of emulsifier as in Example 1 were used to carry out a normal polymerization method without dividing into first-stage polymerization and second-stage polymerization. It will be small. Further, even if the amount of emulsifier is reduced in this system, it is not possible to obtain particles having a large particle size as in the present invention. Comparative Example 2 is an example in which polystyrene particles were polymerized by the same ordinary polymerization method with the aim of obtaining a particle size as large as possible, but about 0.37 μm was a practical limit. Comparative Example 3 is an example in which the ratio of the carboxylic acid monomer in the monomer of the first-stage polymerization is too small, and the polymerization stability is significantly deteriorated, and the agglomerates filtered with a 500 Mesh wire mesh are 8.4% (versus polymer). And the particle size distribution was wide.

[Table 1]

Evaluation Example (Evaluation of Physical Adsorption of Protein and Nucleic Acid) The polymer particle dispersion liquid for a physiologically active substance carrier of the present invention prepared in Example 1 was treated with an Eppendorf centrifuge tube (1.5 m).
l) 0.1 ml each (particle solid content 10 mg) in 4 bottles, 1 ml
Centrifugal washing with phosphate saline (PBS) (6,000 rpm x 10 minutes)
After repeating the procedure three times, 20 mg bovine serum albumin, 20 mg human IgG, 20 mg casein or calf D
1 mg of NA (crude purified) was put into PBS to make 1 ml each.
After incubating the above-mentioned particle and protein or the mixed solution of particles and nucleic acid at 25 ° C for 2 hours, centrifugation (6,
(000 rpm × 10 minutes), the supernatant was subjected to UV-absorbance measurement at 220-320 nm to quantify the concentration of protein or nucleic acid in the liquid phase not adsorbed to the particles, and the amount adsorbed to the particles was calculated from this. Pellet was washed 3 times with PBS and finally washed with 0.1 ml
It was dispersed in PBS. Similarly, the particles of Examples 2, 3 and 7 and the particles of Comparative Examples 1 and 2 were evaluated. The particles of Comparative Example 1 are carboxylic acid-modified polymer particles obtained by an ordinary polymerization method, and the particles of Comparative Example 2 are polystyrene particles obtained by an ordinary polymerization method. At this time, since the particles of Comparative Example 1 have a small particle size, centrifugal sedimentation property is very poor.
Sedimentation was insufficient even with a 0 minute ultracentrifuge. The results are shown in Table 2.
Shown in. It can be seen that the polymer particles for a physiologically active substance carrier of the present invention have a significantly smaller physical adsorption amount of proteins and nucleic acids than conventional polystyrene-based carrier particles.

[0017]

[Table 2]

Evaluation Example (Preparation and Evaluation of Chemiluminescent AFP Immunoassay Reagent from Carrier Particles) In order to evaluate the performance of the physiologically active substance carrier particles of the present invention, a chemiluminescent AFP immunoassay is performed by the chemical bonding method as follows. Reagents were prepared and evaluated. 0.1 ml of the particle dispersion of Example 1
(Particle solid content 10 mg) 1 ml Phosphate saline (PBS)
After centrifuging and washing 3 times with, the procedure of adding 0.1 mM hydrochloric acid aqueous solution (pH = 5.5) to the solid and centrifuging it
The particles were washed by repeating this process. Thereafter, 0.1 mg of 5 mg of 1-ethyl-3-dimethylaminopropylcarbodiimide hydrochloride (manufactured by Dojindo Co., Ltd.) was dissolved.
0.1 ml of a mM hydrochloric acid aqueous solution was added, and the mixture was stirred at 40 ° C. for 2 hours, and 0.1 mg of an anti-AFP monoclonal antibody was dissolved.
0.1 ml of a 1 mM aqueous hydrochloric acid solution was added, the mixture was stirred at room temperature for 1 hour, 0.1 ml of a 1% by weight caffeine solution was added, and the mixture was stirred at room temperature for 1 hour.
By stirring for 4 hours, particles having an anti-AFP monoclonal antibody immobilized on the surface of the particles were prepared. Then, the solution containing the AFP antibody particles is subjected to a centrifugation treatment, and a phosphate buffer (PBS) having a pH of 7.2 containing 0.1% by weight of bovine serum albumin (BSA) is added to the solid matter and the centrifugation treatment is carried out. By repeating this operation 3 times, unreacted AFP antibody was removed, and antibody-sensitized particles using the carrier particles of Example 1 were obtained by the chemical bonding method. The final particle solids content was adjusted to 1%. Antibodies were sensitized by the same procedure for the particles of Example 2-6 and Comparative Example 1-3.

AFP antigen, 0, 10, 50, 100, 500 ng / ml was added to 10 μl of the antibody-sensitized particles prepared above, and the mixture was allowed to stand at room temperature for 10 minutes, and then 200 μg of AFP antibody conjugate labeled with alkaline phosphatase. Was added and reacted at room temperature for 10 minutes. The particles were centrifuged 4 times with PBS to remove unreacted material. Finally 100 μl of sedimented solids (particles)
Lumipulse AMPPD substrate solution (adamantyl-1,2-dioxetane phosphate reagent solution, Fujirebio Co., Ltd.)
And the chemiluminescence value was measured after 5 minutes. The results are shown in Table 3.
Shown in. It can be seen that the sensitized particles using the carrier particles of the examples have a low background and can perform highly accurate measurement from low concentration to high concentration. The particles of Comparative Example 1 had a poor centrifugal sedimentation property, and the maximum conditions (10,000
Although centrifugation was performed for 1 hour at (rpm), it could not be evaluated because it could not be sedimented. The carrier particles of Comparative Example 2 do not have a functional group that chemically bonds to the antibody, and only the background value due to nonspecific adsorption of the particles appears. In the case of using the carrier particles of Comparative Example 3, it is possible to quantify the antigen concentration from the chemiluminescence value, but the background is high, and the chemiluminescence value peaks early and the quantifiable range is narrow. This is considered to be because the particle size distribution of the particles of Comparative Example 3 was too wide, which was a problem as a practical test reagent.

[0020]

[Table 3] Note 1: The carrier particles had a poor centrifugal sedimentation property, and the antibody-sensitized particles could not be prepared.

[0021]

According to the present invention, carboxyl group-modified polymer particles having a large particle size and a narrow particle size distribution can be easily and reproducibly obtained in emulsion polymerization. For this reason, it is possible to easily produce even on an industrial scale even with a particle size of, for example, 0.5 μm or more, which has hitherto been difficult with emulsion polymerization, particularly with carboxyl group modification. The carboxyl group-modified particles of the present invention are high-performance polymer particles for physiologically active substance carriers, and in addition to having a large particle diameter and a uniform particle diameter, carboxyl groups are present at a high density on the particle surface, and therefore, the chemical bonding method is used. In addition to being able to bind physiologically active substances as carrier particles with high density, the surface of the particles has high hydrophilicity and less non-specific adsorption. Therefore, by using the polymer particles for a physiologically active substance carrier of the present invention, a highly sensitive and low background test reagent can be produced. By using the carrier particles of the present invention, a latex diagnostic agent with a higher sensitivity and a wider detection concentration range than ever, a specific DNA / RN
Specific nucleic acid-capturing particles for capturing, purifying, and concentrating A, specific protein-separating particles, DNA-transcription control factor protein-collecting particles, and the like can be prepared. Furthermore, if these particles are packed in a column, affinity chromatography for detecting and collecting a specific physiologically active substance can be performed. It is also possible to arrange these particles on a plate and use them. The drug candidate substance is bound to the surface of the polymer particles for a physiologically active substance carrier of the present invention, which is packed in a column, or supported on a filter paper or a thin layer gel, and further spotted on a plate,
A cell lysate or protein can be flowed to separate and separate components having an affinity for particles. This makes it possible to detect a living body part that interacts with the drug candidate substance. Alternatively, conversely, a physiologically active substance such as a specific protein, nucleic acid or sugar chain is bound to the surface of the polymer particles for a physiologically active substance carrier of the present invention, and a column, filter paper, thin layer gel or plate packed with this is used as a drug candidate. A drug substance can be screened by flowing a substance and separating / separating components having an affinity for particles.

Claims (4)

[Claims] 1. A water-soluble polymerizable carboxylic acid monomer
Production of polymer particles, characterized in that 0% by weight or more of a polymerizable monomer is polymerized in an aqueous medium in the presence of a water-soluble radical initiator, and the vinyl monomer is emulsion-polymerized in the presence of the obtained polymer. Method. 2. The emulsifier concentration in water in emulsion polymerization is 50.
The production method according to claim 1, which is 0 ppm (weight unit) or less. 3. Polymer particles obtainable by the method according to claim 1. 4. A physiologically active substance carrier comprising the polymer particles according to claim 3.